31.1 SCOPE vs STOP

- Outcomes: Prolactin, hPL, GH2, Insulin, HOME-IR, glucose (all outcomes log-transformed)
- Independent variables: Study, GDM_new, BMI, Ethnicity (Caucasian/non-Caucasian), smoking (yes/no), GA at sampling
- Model fitted: LME or GEE model
      log(hormones) ~ Study + GA at sampling + Study:GA at sampling
      Random intercepts for Study ID and Plate 

#outc_ls <- c("Prolactin","HPL","GH2")
outc_ls <- c(hormone_var,insulin_var)
outc2 <- preg_out

# fit LME
fit_ls <- lapply(outc_ls,function(outc){
    if(outc%in%hormone_var){ #LME for hormones
     fit_eq <- as.formula(paste0("log(",outc,")~ Study + ",outc2," + BMI + Ethnicity_cauc + f10c_any_cig_1st_vst + GA_samp + Study*",outc2," + (1|Study.ID) + (1|Assay.",outc,")"))
     fit <- eval(bquote(lmer(.(fit_eq),data=dat_run)))}
    if(outc%in%insulin_var){ #GEE for insulin
        fit_eq <- as.formula(paste0("log(",outc,")~ Study + ",outc2,"+BMI+Ethnicity_cauc+f10c_any_cig_1st_vst+GA_samp+Study*",outc2))
        dat_tmp <- na.omit(dat_run[with(dat_run,order(Study,Study.ID)),c("Study","Study.ID","GA_samp","BMI","Ethnicity_cauc","f10c_any_cig_1st_vst",outc,outc2)])
        fit <- eval(bquote(geeglm(.(fit_eq),data=dat_tmp,id=Study.ID,corstr="independence")))}
             return(fit)})
names(fit_ls) <- outc_ls

# Type III SS
anova_ls <- lapply(fit_ls,function(fit){
               if(!any(class(fit)%in%"gee")){return(Anova(fit,type="III"))}
               if(any(class(fit)%in%"gee")){return(joint_tests(fit,cov.reduce=symmint(0)))}})

31.1.1 Global tests

Type III ANOVA on main and interaction effects, and LM model summaries.

Prolactin
Chisq Df Pr(>Chisq)
(Intercept) 186.2873571 1 <0.0001 ***
Study 2.3744735 1 0.1 ns
GDM_new 0.8352147 1 0.4 ns
BMI 2.3632920 1 0.1 ns
Ethnicity_cauc 89.8462847 1 <0.0001 ***
f10c_any_cig_1st_vst 27.6014746 1 <0.0001 ***
GA_samp 145.4047280 1 <0.0001 ***
Study:GDM_new 2.0357209 1 0.2 ns
HPL
Chisq Df Pr(>Chisq)
(Intercept) 114.7698430 1 <0.0001 ***
Study 7.2736070 1 0.007 **
GDM_new 1.2866802 1 0.3 ns
BMI 122.0690428 1 <0.0001 ***
Ethnicity_cauc 2.9326031 1 0.09 ns
f10c_any_cig_1st_vst 0.2523666 1 0.6 ns
GA_samp 2038.4734597 1 <0.0001 ***
Study:GDM_new 1.9535696 1 0.2 ns
GH2
Chisq Df Pr(>Chisq)
(Intercept) 222.6039862 1 <0.0001 ***
Study 0.8028006 1 0.4 ns
GDM_new 1.2852257 1 0.3 ns
BMI 27.8356406 1 <0.0001 ***
Ethnicity_cauc 0.6462443 1 0.4 ns
f10c_any_cig_1st_vst 0.4132299 1 0.5 ns
GA_samp 862.5535317 1 <0.0001 ***
Study:GDM_new 3.4900314 1 0.06 ns
Insulin
model term df1 df2 F.ratio Chisq p.value
1 Study 1 Inf 21.941 21.941 <0.0001 ***
3 GDM_new 1 Inf 32.023 32.023 <0.0001 ***
4 BMI 1 Inf 228.774 228.774 <0.0001 ***
5 Ethnicity_cauc 1 Inf 16.948 16.948 <0.0001 ***
6 f10c_any_cig_1st_vst 1 Inf 0.127 0.127 0.7 ns
7 GA_samp 1 Inf 0.547 0.547 0.5 ns
2 Study:GDM_new 1 Inf 4.128 4.128 0.04 *
HOMA.IR
model term df1 df2 F.ratio Chisq p.value
1 Study 1 Inf 35.890 35.890 <0.0001 ***
3 GDM_new 1 Inf 29.826 29.826 <0.0001 ***
4 BMI 1 Inf 225.782 225.782 <0.0001 ***
5 Ethnicity_cauc 1 Inf 17.023 17.023 <0.0001 ***
6 f10c_any_cig_1st_vst 1 Inf 0.075 0.075 0.8 ns
7 GA_samp 1 Inf 0.242 0.242 0.6 ns
2 Study:GDM_new 1 Inf 4.391 4.391 0.04 *
GLUC3_mmol.L
model term df1 df2 F.ratio Chisq p.value
1 Study 1 Inf 54.379 54.379 <0.0001 ***
3 GDM_new 1 Inf 3.763 3.763 0.05 ns
4 BMI 1 Inf 8.487 8.487 0.004 **
5 Ethnicity_cauc 1 Inf 1.174 1.174 0.3 ns
6 f10c_any_cig_1st_vst 1 Inf 0.002 0.002 1.0 ns
7 GA_samp 1 Inf 0.289 0.289 0.6 ns
2 Study:GDM_new 1 Inf 1.683 1.683 0.2 ns

31.1.2 Model Summary

Ratio of Geometric means (95% CI)

Prolactin
Var Effect P
(Intercept) 2.88 (2.47, 3.30) <0.0001
StudySTOP -0.10 (-0.22, 0.03) 0.12
GDM_newGDM -0.09 (-0.29, 0.11) 0.36
BMI -0.00 (-0.01, 0.00) 0.12
Ethnicity_caucNo 0.46 (0.37, 0.56) <0.0001
f10c_any_cig_1st_vstYes -0.23 (-0.32, -0.14) <0.0001
GA_samp 0.14 (0.12, 0.16) <0.0001
StudySTOP:GDM_newGDM 0.16 (-0.06, 0.37) 0.15
HPL
Var Effect P
(Intercept) 1.18 (0.96, 1.39) <0.0001
StudySTOP 0.09 (0.02, 0.15) 0.007
GDM_newGDM -0.06 (-0.15, 0.04) 0.26
BMI -0.02 (-0.02, -0.01) <0.0001
Ethnicity_caucNo 0.05 (-0.01, 0.10) 0.09
f10c_any_cig_1st_vstYes 0.01 (-0.03, 0.06) 0.62
GA_samp 0.29 (0.27, 0.30) <0.0001
StudySTOP:GDM_newGDM 0.08 (-0.03, 0.19) 0.16
GH2
Var Effect P
(Intercept) -2.25 (-2.54, -1.95) <0.0001
StudySTOP -0.04 (-0.13, 0.05) 0.37
GDM_newGDM -0.09 (-0.23, 0.06) 0.26
BMI -0.01 (-0.01, -0.01) <0.0001
Ethnicity_caucNo 0.03 (-0.04, 0.10) 0.42
f10c_any_cig_1st_vstYes 0.02 (-0.04, 0.09) 0.52
GA_samp 0.26 (0.24, 0.27) <0.0001
StudySTOP:GDM_newGDM 0.16 (-0.01, 0.32) 0.06
Insulin
Var Effect P
(Intercept) 1.07 (0.54, 1.60) <0.0001
StudySTOP -0.31 (-0.48, -0.14) 0.0003
GDM_newGDM 0.55 (0.31, 0.79) <0.0001
BMI 0.05 (0.05, 0.06) <0.0001
Ethnicity_caucNo 0.30 (0.16, 0.45) <0.0001
f10c_any_cig_1st_vstYes -0.02 (-0.15, 0.10) 0.72
GA_samp 0.01 (-0.02, 0.04) 0.46
StudySTOP:GDM_newGDM -0.28 (-0.55, -0.01) 0.04
HOMA.IR
Var Effect P
(Intercept) -0.38 (-0.94, 0.17) 0.18
StudySTOP -0.46 (-0.64, -0.28) <0.0001
GDM_newGDM 0.62 (0.34, 0.90) <0.0001
BMI 0.06 (0.05, 0.06) <0.0001
Ethnicity_caucNo 0.32 (0.17, 0.47) <0.0001
f10c_any_cig_1st_vstYes -0.02 (-0.15, 0.12) 0.78
GA_samp 0.01 (-0.03, 0.04) 0.62
StudySTOP:GDM_newGDM -0.33 (-0.64, -0.02) 0.04
GLUC3_mmol.L
Var Effect P
(Intercept) 1.65 (1.53, 1.76) <0.0001
StudySTOP -0.14 (-0.18, -0.11) <0.0001
GDM_newGDM 0.09 (-0.02, 0.20) 0.09
BMI 0.00 (0.00, 0.00) 0.004
Ethnicity_caucNo 0.01 (-0.01, 0.04) 0.28
f10c_any_cig_1st_vstYes 0.00 (-0.03, 0.03) 0.97
GA_samp -0.00 (-0.01, 0.01) 0.59
StudySTOP:GDM_newGDM -0.07 (-0.18, 0.04) 0.19

31.1.3 Diagnostics

Model diagnositcs.

Diagnositcs for PRL (ng/ml)

Diagnositcs for hPL (μg/ml)

Diagnositcs for GH2 (ng/ml)

Diagnositcs for Insulin (uU/L)

Diagnositcs for HOMA-IR

Diagnositcs for Glucose (mmol/L)

31.1.4 Results

31.1.4.1 Estimated means

Estimated marginal means (or adjusted means) adjusted for GA at sampling, BMI, ethnicity and smoking.

Prolactin
Study GDM_new response SE df lower.CL upper.CL
SCOPE Uncomplicated 109.56262 9.305789 118.0932 92.60115 129.6309
STOP Uncomplicated 99.54973 7.854561 88.1698 85.10303 116.4488
SCOPE GDM 99.89480 12.472731 445.2661 78.15798 127.6769
STOP GDM 106.18421 9.423807 137.5003 89.09337 126.5536
HPL
Study GDM_new response SE df lower.CL upper.CL
SCOPE Uncomplicated 89.30254 2.778154 308.6675 83.99997 94.93983
STOP Uncomplicated 97.65092 2.612781 168.6963 92.62681 102.94753
SCOPE GDM 84.38702 4.573660 701.9769 75.86859 93.86189
STOP GDM 99.76871 3.433946 352.9937 93.23866 106.75611
GH2
Study GDM_new response SE df lower.CL upper.CL
SCOPE Uncomplicated 2.304031 0.0891074 713.3547 2.135564 2.485789
STOP Uncomplicated 2.212179 0.0685501 355.4472 2.081390 2.351187
SCOPE GDM 2.115925 0.1647247 1117.7141 1.816195 2.465121
STOP GDM 2.372943 0.1005954 556.9857 2.183353 2.578995
Insulin
Study GDM_new response SE df asymp.LCL asymp.UCL
SCOPE Uncomplicated 16.35528 1.1990823 Inf 14.16616 18.88267
STOP Uncomplicated 12.00574 0.6450841 Inf 10.80569 13.33905
SCOPE GDM 28.32869 3.5746105 Inf 22.12173 36.27722
STOP GDM 15.68505 1.1803706 Inf 13.53409 18.17785
HOMA.IR
Study GDM_new response SE df asymp.LCL asymp.UCL
SCOPE Uncomplicated 4.011720 0.3145035 Inf 3.440326 4.678014
STOP Uncomplicated 2.526515 0.1430172 Inf 2.261197 2.822965
SCOPE GDM 7.432129 1.0767853 Inf 5.594857 9.872734
STOP GDM 3.354657 0.2712629 Inf 2.862983 3.930770
GLUC3_mmol.L
Study GDM_new response SE df asymp.LCL asymp.UCL
SCOPE Uncomplicated 5.467687 0.0818211 Inf 5.309650 5.630429
STOP Uncomplicated 4.746897 0.0485391 Inf 4.652709 4.842992
SCOPE GDM 6.005111 0.2972873 Inf 5.449814 6.616988
STOP GDM 4.849296 0.0683255 Inf 4.717212 4.985078

31.1.5 Comparisons

Prolactin
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated) 0.909 0.057 1440.121 0.804 1.027 0.124 ns
STOP/SCOPE (GDM_new) 1.063 0.122 1271.507 0.849 1.330 0.594 ns
GDM_new/Uncomplicated (SCOPE) 0.912 0.092 1206.203 0.748 1.112 0.361 ns
GDM_new/Uncomplicated (STOP) 1.067 0.056 1412.722 0.963 1.182 0.217 ns
HPL
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated) 1.093 0.036 1449.240 1.025 1.167 0.007 **
STOP/SCOPE (GDM_new) 1.182 0.069 1046.878 1.054 1.326 0.004 **
GDM_new/Uncomplicated (SCOPE) 0.945 0.047 734.683 0.857 1.042 0.257 ns
GDM_new/Uncomplicated (STOP) 1.022 0.029 1437.110 0.966 1.081 0.454 ns
GH2
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated) 0.960 0.044 1294.983 0.878 1.050 0.370 ns
STOP/SCOPE (GDM_new) 1.121 0.097 1340.588 0.947 1.328 0.184 ns
GDM_new/Uncomplicated (SCOPE) 0.918 0.069 1260.805 0.793 1.064 0.257 ns
GDM_new/Uncomplicated (STOP) 1.073 0.043 1494.387 0.992 1.159 0.077 ns
Insulin
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated) 0.734 0.063 Inf 0.621 0.868 0.0003 ***
STOP/SCOPE (GDM_new) 0.554 0.080 Inf 0.417 0.735 <0.0001 ***
GDM_new/Uncomplicated (SCOPE) 1.732 0.211 Inf 1.364 2.199 <0.0001 ***
GDM_new/Uncomplicated (STOP) 1.306 0.094 Inf 1.134 1.505 0.0002 ***
HOMA.IR
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated) 0.630 0.057 Inf 0.527 0.752 <0.0001 ***
STOP/SCOPE (GDM_new) 0.451 0.073 Inf 0.328 0.621 <0.0001 ***
GDM_new/Uncomplicated (SCOPE) 1.853 0.264 Inf 1.402 2.448 <0.0001 ***
GDM_new/Uncomplicated (STOP) 1.328 0.103 Inf 1.141 1.545 0.0002 ***
GLUC3_mmol.L
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated) 0.868 0.016 Inf 0.838 0.899 <0.0001 ***
STOP/SCOPE (GDM_new) 0.808 0.039 Inf 0.734 0.889 <0.0001 ***
GDM_new/Uncomplicated (SCOPE) 1.098 0.061 Inf 0.984 1.225 0.093 ns
GDM_new/Uncomplicated (STOP) 1.022 0.014 Inf 0.994 1.050 0.132 ns

31.1.5.1 Barplots

31.1.6 Comparisons by Timepoint

Prolactin
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated)|10wks 0.909 0.057 1440.121 0.804 1.027 0.124 ns
STOP/SCOPE (GDM_new)|10wks 1.063 0.122 1271.507 0.849 1.330 0.594 ns
GDM_new/Uncomplicated (SCOPE)|10wks 0.912 0.092 1206.203 0.748 1.112 0.361 ns
GDM_new/Uncomplicated (STOP)|10wks 1.067 0.056 1412.722 0.963 1.182 0.217 ns
STOP/SCOPE (Uncomplicated)|16wks 0.909 0.057 1440.121 0.804 1.027 0.124 ns
STOP/SCOPE (GDM_new)|16wks 1.063 0.122 1271.507 0.849 1.330 0.594 ns
GDM_new/Uncomplicated (SCOPE)|16wks 0.912 0.092 1206.203 0.748 1.112 0.361 ns
GDM_new/Uncomplicated (STOP)|16wks 1.067 0.056 1412.722 0.963 1.182 0.217 ns
16wks/10wks (Uncomplicated)|SCOPE 2.320 0.162 1435.177 2.023 2.660 <0.0001 ***
16wks/10wks (GDM_new)|SCOPE 2.320 0.162 1435.177 2.023 2.660 <0.0001 ***
16wks/10wks (Uncomplicated)|STOP 2.320 0.162 1435.177 2.023 2.660 <0.0001 ***
16wks/10wks (GDM_new)|STOP 2.320 0.162 1435.177 2.023 2.660 <0.0001 ***
HPL
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated)|10wks 1.093 0.036 1449.240 1.025 1.167 0.007 **
STOP/SCOPE (GDM_new)|10wks 1.182 0.069 1046.878 1.054 1.326 0.004 **
GDM_new/Uncomplicated (SCOPE)|10wks 0.945 0.047 734.683 0.857 1.042 0.257 ns
GDM_new/Uncomplicated (STOP)|10wks 1.022 0.029 1437.110 0.966 1.081 0.454 ns
STOP/SCOPE (Uncomplicated)|16wks 1.093 0.036 1449.240 1.025 1.167 0.007 **
STOP/SCOPE (GDM_new)|16wks 1.182 0.069 1046.878 1.054 1.326 0.004 **
GDM_new/Uncomplicated (SCOPE)|16wks 0.945 0.047 734.683 0.857 1.042 0.257 ns
GDM_new/Uncomplicated (STOP)|16wks 1.022 0.029 1437.110 0.966 1.081 0.454 ns
16wks/10wks (Uncomplicated)|SCOPE 5.574 0.212 1454.688 5.173 6.006 <0.0001 ***
16wks/10wks (GDM_new)|SCOPE 5.574 0.212 1454.688 5.173 6.006 <0.0001 ***
16wks/10wks (Uncomplicated)|STOP 5.574 0.212 1454.688 5.173 6.006 <0.0001 ***
16wks/10wks (GDM_new)|STOP 5.574 0.212 1454.688 5.173 6.006 <0.0001 ***
GH2
contrast ratio SE df lower.CL upper.CL p.value
STOP/SCOPE (Uncomplicated)|10wks 0.960 0.044 1294.983 0.878 1.050 0.370 ns
STOP/SCOPE (GDM_new)|10wks 1.121 0.097 1340.588 0.947 1.328 0.184 ns
GDM_new/Uncomplicated (SCOPE)|10wks 0.918 0.069 1260.805 0.793 1.064 0.257 ns
GDM_new/Uncomplicated (STOP)|10wks 1.073 0.043 1494.387 0.992 1.159 0.077 ns
STOP/SCOPE (Uncomplicated)|16wks 0.960 0.044 1294.983 0.878 1.050 0.370 ns
STOP/SCOPE (GDM_new)|16wks 1.121 0.097 1340.588 0.947 1.328 0.184 ns
GDM_new/Uncomplicated (SCOPE)|16wks 0.918 0.069 1260.805 0.793 1.064 0.257 ns
GDM_new/Uncomplicated (STOP)|16wks 1.073 0.043 1494.387 0.992 1.159 0.077 ns
16wks/10wks (Uncomplicated)|SCOPE 4.671 0.245 1432.164 4.214 5.177 <0.0001 ***
16wks/10wks (GDM_new)|SCOPE 4.671 0.245 1432.164 4.214 5.177 <0.0001 ***
16wks/10wks (Uncomplicated)|STOP 4.671 0.245 1432.164 4.214 5.177 <0.0001 ***
16wks/10wks (GDM_new)|STOP 4.671 0.245 1432.164 4.214 5.177 <0.0001 ***
Insulin
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated)|10wks 0.734 0.063 Inf 0.621 0.868 0.0003 ***
STOP/SCOPE (GDM_new)|10wks 0.554 0.080 Inf 0.417 0.735 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|10wks 1.732 0.211 Inf 1.364 2.199 <0.0001 ***
GDM_new/Uncomplicated (STOP)|10wks 1.306 0.094 Inf 1.134 1.505 0.0002 ***
STOP/SCOPE (Uncomplicated)|16wks 0.734 0.063 Inf 0.621 0.868 0.0003 ***
STOP/SCOPE (GDM_new)|16wks 0.554 0.080 Inf 0.417 0.735 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|16wks 1.732 0.211 Inf 1.364 2.199 <0.0001 ***
GDM_new/Uncomplicated (STOP)|16wks 1.306 0.094 Inf 1.134 1.505 0.0002 ***
16wks/10wks (Uncomplicated)|SCOPE 1.075 0.105 Inf 0.887 1.303 0.460 ns
16wks/10wks (GDM_new)|SCOPE 1.075 0.105 Inf 0.887 1.303 0.460 ns
16wks/10wks (Uncomplicated)|STOP 1.075 0.105 Inf 0.887 1.303 0.460 ns
16wks/10wks (GDM_new)|STOP 1.075 0.105 Inf 0.887 1.303 0.460 ns
HOMA.IR
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated)|10wks 0.630 0.057 Inf 0.527 0.752 <0.0001 ***
STOP/SCOPE (GDM_new)|10wks 0.451 0.073 Inf 0.328 0.621 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|10wks 1.853 0.264 Inf 1.402 2.448 <0.0001 ***
GDM_new/Uncomplicated (STOP)|10wks 1.328 0.103 Inf 1.141 1.545 0.0002 ***
STOP/SCOPE (Uncomplicated)|16wks 0.630 0.057 Inf 0.527 0.752 <0.0001 ***
STOP/SCOPE (GDM_new)|16wks 0.451 0.073 Inf 0.328 0.621 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|16wks 1.853 0.264 Inf 1.402 2.448 <0.0001 ***
GDM_new/Uncomplicated (STOP)|16wks 1.328 0.103 Inf 1.141 1.545 0.0002 ***
16wks/10wks (Uncomplicated)|SCOPE 1.052 0.109 Inf 0.859 1.289 0.623 ns
16wks/10wks (GDM_new)|SCOPE 1.052 0.109 Inf 0.859 1.289 0.623 ns
16wks/10wks (Uncomplicated)|STOP 1.052 0.109 Inf 0.859 1.289 0.623 ns
16wks/10wks (GDM_new)|STOP 1.052 0.109 Inf 0.859 1.289 0.623 ns
GLUC3_mmol.L
contrast ratio SE df asymp.LCL asymp.UCL p.value
STOP/SCOPE (Uncomplicated)|10wks 0.868 0.016 Inf 0.838 0.899 <0.0001 ***
STOP/SCOPE (GDM_new)|10wks 0.808 0.039 Inf 0.734 0.889 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|10wks 1.098 0.061 Inf 0.984 1.225 0.093 ns
GDM_new/Uncomplicated (STOP)|10wks 1.022 0.014 Inf 0.994 1.050 0.132 ns
STOP/SCOPE (Uncomplicated)|16wks 0.868 0.016 Inf 0.838 0.899 <0.0001 ***
STOP/SCOPE (GDM_new)|16wks 0.808 0.039 Inf 0.734 0.889 <0.0001 ***
GDM_new/Uncomplicated (SCOPE)|16wks 1.098 0.061 Inf 0.984 1.225 0.093 ns
GDM_new/Uncomplicated (STOP)|16wks 1.022 0.014 Inf 0.994 1.050 0.132 ns
16wks/10wks (Uncomplicated)|SCOPE 0.988 0.022 Inf 0.946 1.032 0.591 ns
16wks/10wks (GDM_new)|SCOPE 0.988 0.022 Inf 0.946 1.032 0.591 ns
16wks/10wks (Uncomplicated)|STOP 0.988 0.022 Inf 0.946 1.032 0.591 ns
16wks/10wks (GDM_new)|STOP 0.988 0.022 Inf 0.946 1.032 0.591 ns

31.1.6.1 Barplots by Timepoint

31.1.6.2 Plots for GA